L-Ascorbic acid (vitamin C) is produced commercially by combined chemical and fermentation processes starting from glucose or sorbose. A common intermediate generated in the commercial process is 2-keto-L-gulonic acid (KLG), or its protected form, diacetone-2-keto-L-gulonic acid. The conversion of 2-keto-L-gulonic acid to L-ascorbic acid may be carried out by esterification with methanol, followed by cyclization using stoichiometric amounts of a base, in a methodology derived from the original Reichstein process (T. Reichstein, A. Grussner, Helv. Chim. Acta 17, pp. 311-314, 1934). Alternatively, diacetone-2-keto-L-gulonic acid may be cyclized directly, with a loss of acetone followed by consecutive lactonization and enolization, to form ascorbic acid. Direct cyclization of diacetone-2-keto-L-gulonic acid requires extensive purification for recovery of the acetone and other by-products generated.
Modifications to the Reichstein process have focused on removal or simplification of many of the chemical processing steps required for the production of 2-keto-L-gulonic acid. Improvements include controlled esterification of 2-keto-L-gulonic acid and subsequent removal of unesterified starting material (U.S. Pat. No. 5,128,487), as well as improved integration of esterification with subsequent cyclization (U.S. Pat. No. 5,391,770).
Efforts have also been directed to acid catalysis (e.g. U.S. Pat. No. 2,462,251; GB 1,222,322; GB 2,034,315; DE 3843389; WO 99/07691; and WO 00/46216) thereby removing the steps of esterification with subsequent based-catalyzed cyclization and reprotonation of the L-ascorbic acid product. In addition, modifications to improve the process such as the use of organic solvents and surfactants have been described (see e.g. U.S. Pat. No. 5,744,618; WO 98/00839; and JP-B 73015931).
An alternative means of producing ascorbic acid from 2-keto-L-gulonic acid involves an aqueous intramolecular cyclization process without the use of copious amounts of acid catalysts (T. Reichstein, Helv. Chim. Acta 17, 1934, pp. 311-328 and BP 428,815). Although aqueous cyclization does not require the extensive purification steps associated with acid catalysis, non-acid catalyzed intramolecular cyclization is associated with relatively low yields. For example, 2-keto-L-gulonic acid may be heated in water saturated with carbon dioxide with a 50% yield after fractional crystallization (U.S. Pat. No. 2,265,121). Also, 2-keto-L-gulonic acid or derivatives of 2-keto-L-gulonic acid may be heated to 130-140° C. in water to generate ascorbic acid with yields approximating 50% (U.S. Pat. No. 2,491,065).
A common problem encountered with conversion of 2-keto-L-gulonic acid to ascorbic acid in water or the presence of acidic solutions is the production of colored solutions from degradation products. These degradation products generally include high molecular weight compounds that accumulate as a function of conversion. Thus, with increasing conversion, solutions tend to become increasingly colored and eventually form insoluble by-products. Generally, methods to decolor ascorbic acid involve adsorption of the colored by-products using carbon or other solid supported agents. Ultimately, the use of large amounts of carbon or other solid decolorizing agents significantly hinders subsequent purification of the L-ascorbic acid product.
Thus, there is a need for improved methods to decolor ascorbic acid produced by aqueous or acid catalysis. In addition, there is a need for a soluble decolorizing agent for those situations where solid decolorizing agents, such as carbon, cannot be used. For example, in highly discolored solutions, the amount of carbon required can be so high as to be impractical. Also, the use of a soluble form of decolorizing agent would be beneficial in situations where impurities are bound covalently to the high molecular weight by-products, thus allowing the colored impurities to be removed by a separate step. By simplifying recovery protocols, soluble additives or agents suitable for removing colored bodies in situ significantly improve ascorbic acid yield.